Menon K P, Neufeld E F
Department of Biological Chemistry, UCLA School of Medicine 90024-1737.
Cell Mol Biol (Noisy-le-grand). 1994 Nov;40(7):999-1005.
Mutations in the gene encoding alpha-L-iduronidase (IDUA) are the cause of Hurler syndrome. Fibroblasts from patients homozygous for nonsense IDUA alleles have much reduced mRNA detectable by Northern analysis, as has been observed in many other instances of premature translation termination. Yet RT-PCR (reverse transcription followed by PCR amplification) showed a normal level of a segment covering exons 1 and 2 in Hurler cells homozygous for alleles bearing the nonsense mutations, Q70X or W402X. The 3' end of the segment was between exons 2 and 4. The results indicate that the nonsense RNA was degraded to fragment(s), independent of the position of the mutation (exon 2 or exon 9, respectively). Treatment of the cells with cycloheximide resulted in some increase of intact mRNA, suggesting that translation is required for mRNA degradation.
编码α-L-艾杜糖醛酸酶（IDUA）的基因突变是Hurler综合征的病因。对无义IDUA等位基因纯合的患者成纤维细胞，通过Northern分析可检测到的mRNA大幅减少，这在许多其他过早翻译终止的情况中也有观察到。然而，逆转录聚合酶链反应（RT-PCR，即逆转录后进行PCR扩增）显示，在对携带无义突变Q70X或W402X的等位基因纯合的Hurler细胞中，覆盖外显子1和2的片段水平正常。该片段的3'端位于外显子2和4之间。结果表明，无义RNA被降解为片段，与突变位置无关（分别在外显子2或外显子9）。用环己酰亚胺处理细胞导致完整mRNA有所增加，这表明mRNA降解需要翻译过程。
